Picornaviruses comprise a large group of RNA viruses that cause a multitude of serious illness among humans. Included are meningitis, myocarditis, poliomyelitis, hepatitis, hand-foot-and- mouth disease, and hemorrhagic conjunctivitus. Guanidine has been found to selectively inhibit growth of many picornaviruses at millimolar levels without adversely affecting host cells. Hopefully, this compound will prove to have chemotherapeutic value alone or in combination with other anti-viral compounds. We have recently determined the site of guanidine action with drug resistant mutants of poliovirus and plan to determine the mechanism whereby RNA synthesis of virus is blocked. We will determine 1 what amino acid changes confer guanidine resistance or dependence to virus, 2 whether the guanidine marker is restricted to several domains in the 2C locus, and 3 whether amino acid sequences that confer guanidine resistance are identical among types 1 and 3 polioviruses.